Mode of action of the schistosomicide hycanthone: site of DNA alkylation.
Condensation of hycanthone N-methylcarbamate (HNMC) with deoxyguanosine (dG) furnished a mixture of the N-1 and N2 adducts which were purified and characterized as their acetates. Condensation of HNMC with thymidine (T) gave the N-3 adduct in poor yield. Adenosine (A) and cytidine (C) did not react with HNMC. Incubation of schistosomes with either [3H]hycanthone (HC) or [3H]HNMC furnished DNA to which [3H]HC was covalently bound. The alkylated DNA was degraded enzymically and the radiolabeled nucleosides were separated using HPLC. Two major peaks were observed which coincided in retention time with the synthetic N-1 and N2 alkylated dG. Alkylated T was absent. Thus, the site of alkylation of DNA by either HC or HNMC is dG.
Archer
S
S
Department of Chemistry, Rensselaer Polytechnic Institute, Troy, NY 12180-3590.
el-Hamouly
W
W
Seyed-Mozaffari
A
A
Butler
R H
RH
Pica-Mattoccia
L
L
Cioli
D
D
D000478:Alkylation; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D003849:Deoxyguanosine / Q000378:metabolism / Q000494:pharmacology; D006826:Hycanthone / Q000378:metabolism / Q000494:pharmacology*; D015394:Molecular Structure; D012550:Schistosoma mansoni / Q000187:drug effects*
D006826:Hycanthone; D004247:DNA; D003849:Deoxyguanosine